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HELVETICA CHIMICA ACTA- Vol. 60, Fasc. 6 (1977) - Nr. 197

197. New Indigo Syntheses

Preliminary Communication by Jacques Gosteli Woodward Research Institute, CH-4002 Base1 Dedicated to Professor R. B. Woodward on the occasion of his sixtieth birthday anniversary
(11. VII. 77)

Three novel routes for the preparation of the dyestuff indigo are described. Two of the methods usk isatoic anhydride, the third one styrene as starting materials. Key reactions are acylation of both dimsyl and nitromethane anions, Pummerer rearrangement and Nef reaction. A novel nitration of styrene is the basis of the third method.

The popularity of certain fashion wear has led to a vigorous comeback of the vat dye indigo 1 in recent years. This coloring matter, known for some fourty centuries, was originally obtained from plants of Indigofera species. Baeyers determination of the constitution and first synthesis [I a, b] gave rise to a period of frantic search for practical syntheses in the chemical industry of the time [2]. The end was most successfully achieved by Heumanns indoxyl melt process of 1890 [2] [3], nowadays in much improved version, still the method practised on large scale. 3 H-Indol-3-one (2), recognized as most likely though elusive intermediate in syntheses of indigo [l c] suggested novel approaches to the dye to be described herein.

An equally fugitive compound and hence undescribed in the literature is the hypothetical hydrolysis product of 2, o-aminophenylglyoxal (3). The corresponding dimethyl acetal, however, can be prepared and it rapidly and quantitatively converts to indigo on acidic hydrolysis [4]. The approaches to 3 to be outlined first feature as common idea the combination of the two synthons anthranoyl cation 4 (bearing a protecting group on nitrogen to prevent self-condensation) and formyl anion 5 .


HELVETICA CHIMICA ACTA - Vol. 60, Fasc. 6 (1977) - Nr. 197

However, when 6 was reacted with two equivalents of nitromethane in dimethylsulfoxide solution at 50' for 12 h in the presence of 0.6 equiv. of anhydrous potassium carbonate o-amino-o-nitroacetophenone1)(9), m.p. 110-1 1lo, was obtained in 57% yield4). On warming 9 in 4~ aqueous HCl initial darkening followed by precipitation

of 1 was observed. Doubtless, the key step of this transformation is a Nef reaction in the course of which the nitromethyl group of 9 is converted to a carboxaldehyde function or an equivalent thereof. Both in terms of yield and purity of 1, the conversion 9 to 1 is again advantageously carried out with intercalary acetylation of the amino group. lo1), m.p. 180-182', was prepared by heating a benzene solution of 9 containing acetic anhydride. When crude 10 obtained by evaporation of solvent and excess reagent was warmed in 2~ HC1 to 75-80' for 3 h 1 was isolated in 88% yield from 9. Alternatively, 10 could be prepared from 2-methyl-1,3-benzoxazin-4-one, 11 [7], albeit in low yield, by treating 11 in hexamethylphosphoric amide solution at 80' with two equivalents of nitromethane in the presence of anhydrous sodium carbonate. The main product of the reaction was found to be the anthranilic acid derivative 121), m.p. 168-170'. It appears that 11 reacts only partially in the sense predicted for expression 4.





Still another route to 1 was hinted by the finding of Harley-Mason [8] that the dinitro-hydroxy derivative 13 yields indigo in high yield when reduced with aqueous sodium dithionite. 13 had been obtained previously by Thiele [9] from o-nitrobenzaldehyde. This author also had noted the formation of a blue color on treatment of 13 with ferrous ions.



4 ,

9 proved somewhat unstable under the conditions of the experiment and, in particular, in strongly basic media. When 9 was warmed in aqueous 1 N sodium hydroxide anthranilic acid was formed rapidly in a manner reminiscent of the haloform cleavage.